Cardiovascular effects of cocaine are being extensively studied using various species of animals as model systems. Recent investigations have focused on the cocaine metabolites and pyrolysis products, as well as drug interactions. With repeated use of cocaine, the effects of the metabolites may play a more prominent role in the overall effect of cocaine. With the widespread use of "crack" cocaine, the possibility that the pyrolysis products may contribute to cocaine's cardiovascular effects must also be considered. In studies with anesthetized rabbit preparations, injections of small doses of cocaine in the hindbrain of the rabbit produced clear decreases in heart rate, blood pressure and respiratory rate. The same doses give i.v. were without effect, indicating that these depressant effects of cocaine were mediated in the hindbrain. The cocaine metabolite cocaethylene had similar effects, although its effect on respiration was of longer duration. Norcocaine decreased blood pressure but did not affect respiration. The cocaine pyrolysis products also decreased blood pressure and heart rate but increased respiration. The effects of these compounds were comparable when delivered either into the hindbrain or when given i.v., indicating that their effects were not mediated in the hindbrain. These results suggest that the cocaine pyrolysis products do not share a common mechanism of action with cocaine. Cocaine is often used in combination with other drugs. One frequent drug-use combination is that of heroin and cocaine. When given to anesthetized rabbits as a slow, continuous i.v. infusion, cocaine decreased heart rate and blood pressure and increased respiratory rate at higher doses. Heroin also produced decreases in blood pressure and heart rate while decreasing respiration. When given in combination, the hemodynamic effects were exacerbated while cocaine failed to antagonize the respiratory depressant effect of heroin. These results suggest that this drug combination may lead to greater adverse effects than would be predicted from the effects of these drug alone.